DNA Damage and Repair is a new program formed from the previous program in Molecular Carcinogenesis. This program comprises a group of investigators studying DNA damage using chemical methods such as mass spectrometry and NMR spectroscopy, and investigators studying DNA repair using defined in vitro systems, as well as DNA repair and mutagenesis in intact cells. Overall, the goals of this program are to understand the relationship between DNA damage and carcinogenesis at the molecular level, and to understand how DNA repair pathways can reverse the effects of DNA damage. Ultimately, these studies should allow us to predict the types and frequencies of genetic mutations resulting from a complicated array of DNA damage. We believe that the cooperation among investigators with productive research programs in several aspects of DNA damage, repair and mutagenesis places this program in an unusually strong position to make substantive contributions in understanding fundamentally important aspects of chemical carcinogenesis and cancer chemotherapy. The types of DNA damage studied include oxidative, alkylation and hydrolytic damage, polycyclic hydrocarbons and other aromatic compounds, and ultraviolet light. The repair pathways investigated are nucleotide excision repair, base excision repair, mismatch repair, and recombinational repair pathways. The systems used to study DNA repair and mutagenesis range from yeast to mammalian cells. In future years, in collaboration with other Programs within the Cancer Center, we plan to investigate the relationships between DNA damage and epigenetic changes, relationships between DNA repair defects and increased cancer susceptibility, and strategies to exploit DNA repair defects present in human tumors as targets for chemotherapy. The 10 Full and 4 Associate Members of the Program in DNA Damage and Repair have published 230 articles, books, book chapters, etc., since the last competitive grant review. Of these, 27 are intraprogrammatic and 32 are interprogrammatic publications.